Prevention of chemotherapy-induced alopecia in rats by CDK inhibitors

  • Science. 2001 Jan 5;291(5501):134-7. doi: 10.1126/science.291.5501.134.
S T Davis  1 ,  B G Benson ,  H N Bramson ,  D E Chapman ,  S H Dickerson ,  K M Dold ,  D J Eberwein ,  M Edelstein ,  S V Frye ,  R T Gampe Jr ,  R J Griffin ,  P A Harris ,  A M Hassell ,  W D Holmes ,  R N Hunter ,  V B Knick ,  K Lackey ,  B Lovejoy ,  M J Luzzio ,  D Murray ,  P Parker ,  W J Rocque ,  L Shewchuk ,  J M Veal ,  D H Walker ,  L F Kuyper
Affiliations
  • 1. Department of Cancer Biology, Glaxo Wellcome Research and Development, Research Triangle Park, NC 27709, USA. [email protected]
PMID: 11141566 DOI: 10.1126/science.291.5501.134
Abstract

Most traditional cytotoxic Anticancer agents ablate the rapidly dividing epithelium of the hair follicle and induce alopecia (hair loss). Inhibition of cyclin-dependent kinase 2 (CDK2), a positive regulator of eukaryotic cell cycle progression, may represent a therapeutic strategy for prevention of chemotherapy-induced alopecia (CIA) by arresting the cell cycle and reducing the sensitivity of the epithelium to many cell cycle-active antitumor agents. Potent small-molecule inhibitors of CDK2 were developed using structure-based methods. Topical application of these compounds in a neonatal rat model of CIA reduced hair loss at the site of application in 33 to 50% of the Animals. Thus, inhibition of CDK2 represents a potentially useful approach for the prevention of CIA in Cancer patients.

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